The following prior art publications are considered as relevant for an understanding of the invention. The publications are referred to herein by their number in the following list:    1. “Selectively cross linked Hyaluronic acid hydrogels for sustained release formulation for Erythropoietyn”, K. Motokawa, S. K. Hahn, T. Nakamura, H. Miyamoto, T. Shimoboji, J. of Biomed. Mat. Res., part A, DOI 10.1002, pp 459-465, 2006.    2. Controlled chemical modification of Hyaluronic acid: Synthesis, applications and biodegradations of hydrazide derivatives”, G. D. Prestwich, D. M. Marecak, J. F. Marecek, K. P. Vercruysse, M. R. Ziebell, J. Cont. Rel., vol. 53, pp 93-103, 1998.    3. “Cross-linked hyaluronic acid hydrogel films: New biomaterials for drug delivery”, Y. Lou, K. R. Kirker, G. D. Prestwich, J. Cont. Rel., vol. 69, pp 169-184, 2000.    4. “Sustained release formulation of erythropoietin using hyaluronic acid hydrogels cross-linked by Michael addition”, S. K. Hahn, E. J. Oh, H. Miyamoto, T. Shimobouji, Int. J. of Pharm. 322, pp 44-51, 2006.    5. “Comparison of the effectiveness of four different crosslinking agents with Hyaluronic acid hydrogel films for tissue culture application”, M. N. Collins, C. Birkinshaw, J. of Appl. Pol. Sci., Vol. 104, pp 3183-3191, 2007.    6. U.S. Pat. No. 6,831,172.    7. “Injectable biodegradable hydrogels composed of hyaluronic acid-tyramine conjugates for delivery and tissue engineering”, M. Kurisawa, J. E. Chung, Y. Y. Yang, S. J. Gao, H. Uyama, Chem. Commun., 2005, pp 4312-4314.    8. “Photopolymerized hyaluronic acid-based hydrogels and interpenetrating networks”, Y. D. Park, N. Tirelli, J. A. Hubbell, Biomat. 24, pp 893-900, 2003.    9. “Controlled chemical modification of hyaluronic acid: synthesis, applications, and biodegradation of hydrazide derivatives”, G. D. Prestwich, D. M. Marecak, J. F. Marecek, K. P. Vorcruysse, M. R. Ziebell, J. Con. Rel., 53, pp 93-103, 1998.    10. US patent application #20050177118    11. “Effectiveness of a new novel Hyaluronic-acid gel film in the rat model”, Y. Himeda, H. Kaneko, T. Umeda, Y. Miyata, T. Miyoshi, J. of Gynecologic Surgery, vol 21(2), pp 55-63, 2005.    12. “Characterization of Hyaluronic acid-Arg-Gly-Asp peptide cell attachment matrix”, J. R. Glass, K. T. Dickerson, K. Stecker, J. Polarek, Biomaterials, vol. 17(11), pp 1101-1108, 1996.    13. “Development of photocrosslinkable Hyaluronic acid-polyethylene glycol-peptide composite hydrogels for soft tissue engineering”, J B. Leach, K. A. Bivens, C. N. Collins, C. E. Schmidt, Biomed Mater. Res. 70A, pp 74-82, 2004.
The human skin is the largest organ of the body, accounting for about 16% of the body's weight. It performs many vital roles as both a barrier and a regulating influence between the outside world and the controlled environment within the body.
There are two main layers of skin. The epidermis is made up of keratinocytes, which are stacked on top of each other. The keratinocytes develop at the bottom of the epidermis and rise to the surface, where they are shed as dead, hard, flattened cells. This layer is thus constantly being renewed. Melanocytes and Langerhans cells are other important cells of the epidermis.
The dermis consists mostly of connective tissue and is much thicker than the epidermis. It is responsible for the skin's pliability and mechanical resistance and is also involved in the regulation of body temperature. The dermis supplies the avascular epidermis with nutrients and contains sense organs for touch, pressure, pain and temperature (Meissner's corpuscles, Pacinian corpuscles, free nerve endings), as well as blood vessels, nerve fibers, sebaceous and sweat glands and hair follicles.
The subcutaneous layer is the fatty layer underneath the skin and consists of loose connective tissue and much fat. It acts as a protective cushion, insulates the body by monitoring heat gain and heat loss, and has a strong impact on the way the skin looks.
There are two distinct types of skin aging. Intrinsic aging is genetic in origin, while extrinsic aging is caused by environmental factors, such as exposure to sunlight. Intrinsic aging, also known as the natural aging process, is a continuous process that normally begins in the mid-20s. A number of extrinsic factors often act together with the normal aging process to cause premature aging of the skin. Most premature aging is caused by sun exposure. Other external factors that prematurely age the skin are repetitive facial expressions, gravity, sleeping positions, and smoking.
As the skin ages, the production of cells in the skin slows down and the cells become abnormally shaped, which adversely affects the texture of the skin:                Younger skin has more fat cells in the dermis than older skin. Thus, older skin looks more transparent and thinner than younger skin.        Certain components of the skin become depleted with age. The water-retaining and texture-enhancing elements in the intercellular structure such as ceramides, hyaluronic acids, polysaccharides, glycerin, and many others are exhausted and not replenished. Older skin thus tends to be drier than younger skin.        The skin's support structures, collagen and elastin, deteriorate or become damaged. Wrinkles form in damaged areas of the skin due to the decrease in elastin, collagen, hylauronic acid and other moisturizing reagents.        Older skin is more subject to allergic reactions, sensitivities, and irritation than younger skin due to a weakened immune system.        Dead skin cells do not shed as quickly and the turnover of new skin cells may decrease slightly.        For some unknown reason, the skin continues to grow and expand while the supporting fat tissues of the lower layers of skin and the bones decrease. Simultaneously, the facial muscles lose their shape and firmness. The skin thus begins to sag giving the face a drooping appearance.        
A huge effort and large investment has been made worldwide aimed at fighting skin aging. Trans-dermal application of collagen, vitamins and moisturizing and firming compounds are available. This requires at least daily application of these substances, due to their very short half-time life in the body.
Another approach is subcutaneous injections of dermal fillers. Permanent fillers are based mainly on silicone derivatives or a collagen matrix with non-biodegradable (poly-methylmethacrylate) spheres. The side effects of dermal filling include fibrosis, teratomas and facial distortions due to dislocation of the filler.
Temporary fillers are based on injections of biodegradable compounds such as collagen, synthetic polymers (cross-linked polyacrylamide, usually classified as hydrogels due to their water swelling and retaining properties); and various modifications of cross linked and stabilized hyaluronic acid. These dermal fillers are injected subcutaneously about every 3-8 months.
Autologus fat implementation has also been used, but this involves a painful and slow healing process.
Hyaluronic acid is known as a biomaterial for use as a controlled release drug delivery matrix1, 2, 3, 4), scaffolding for tissue engineering cellular procedures5, 6, and in CA patent 2551121. Use of hyaluronic acid as a biomaterial/tissue engineering matrix utilizes its special properties. It is a soluble, biocompatible polymer, it can be produced from a non-animal source (bacterial fermentation processes) and is produced in a wide range of molecular weights. It is also very easy to chemically modify the HA polymer with various functional groups. It provides a nutritious medium for cell cultures, and its gel form allows control of its flowability. Nevertheless, its most important disadvantage lies in its very short half life time, which, even with an extreme level of cross linking, ranges from few hours to about two weeks7, 8, 9.
Chemical modification of hyaluronic acid and cross-linking often results in loss of solubility, thus reducing ifs injectability. One of the ways to bypass this barrier is to shape the cross linked HA as a film or layered device10, 11/micro particle/bead.
Micro particles of HA disclosed in U.S. Pat. No. 6,969,531, where the particles are processed with chemical reagents (both cross linkers and emulsifying agents, e.g. surfactants).U.S. Pat. No. 7,163,701, discloses HA particles formed in the presence of metal ions.
Linking peptide to a hyaluronic bead or a scaffold is a known approach both as a research tool and as a biomaterial12, 13. Nevertheless, this modification also suffers from an increased hydrophobicity, thus reducing the ability of the compound to be injected.
The ficolins form a group of proteins having collagen-, and fibrinogen-like domains. They were first identified as proteins that bind to TGF-β1. Three types of ficolin have been identified in humans: L-ficolin, H ficolin and M ficolin. A ficolin polypeptide consists of a small N-terminal domain, a collagen-like domain, a neck region, and a fibrinogen-like domain, which shows similarity to the C-terminal halves of the beta and gamma chains of fibrinogen. The collagen-like domain mediates the association of ficolin polypeptides into trimers, and the N-terminal domain contains cysteine residues which permit the covalent assembly of trimers into higher oligomers with a “bouquet-like” appearance. This supramolecular organization resembles that of the collectins, a group of C-type lectins which have a C-type CRD in place of the fibrinogen-like domain found in ficolins. Collectins and ficolins are also functionally similar. The collectin mannose binding protein (MBP) is a serum host defense protein in which the C-type CRDs recognize arrays of GlcNAc and mannose residues on pathogen surfaces. MBP initiates the lectin branch of the complement system via activation of MBP-associated proteases (MASPs), leading to elimination of the target pathogen. Two of the three human ficolins, ficolins L and H, are also serum proteins which bind to pathogen surfaces via interaction with carbohydrates (and probably with other molecules), and trigger complement activation though association with MASPs. Ficolin L also acts as an opsonin, promoting phagocytosis of pathogens by neutrophils. Ficolin L polymorphisms affect serum protein levels and sugar binding and may have pathophysiological implications. The third human ficolin, ficolin M, is found in secretory granules in neutrophils and monocytes, recognizes pathogens in a carbohydrate-dependent manner and activates complement via MASPs. Ficolin M may also act as a phagocytic receptor. Ficolins L and H are produced in the liver, in common with MBP, and ficolins M and H are produced in the lung, like the antimicrobial collectins SP-A and SP-D. Human ficolins and MBP also participate in the recognition and clearance of apoptotic cells. Two ficolins, A and B, are present in mouse. Ficolin B is found in the lysosomes of activated macrophages and is suggested to be the ortholog of ficolin M, but it appears that only ficolin A is associated with MASPs and can activate complement. The mouse ortholog of ficolin H is a pseudogene.